A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy

Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) a...

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Bibliographic Details
Published in:Oncotarget 2016-08, Vol.7 (32), p.52207-52217
Main Authors: Liang, Xiao, Luo, Min, Wei, Xia-Wei, Ma, Cui-Cui, Yang, Yu-Han, Shao, Bin, Liu, Yan-Tong, Liu, Ting, Ren, Jun, Liu, Li, He, Zhi-Yao, Wei, Yu-Quan
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Cell Line, Tumor
Colonic Neoplasms
Drug Delivery Systems - methods
Folate Receptor 1 - metabolism
Genetic Therapy - methods
Interleukin-15 - administration & dosage
Liposomes - administration & dosage
Mice
Mice, Inbred BALB C
Research Paper
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Summary:Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight (P < 0.001) and reduced tumor nodule formation (P < 0.001). Moreover, when compared to other lipoplex-treated mice, F-PLP/pIL15-treated mice showed higher levels of IL15 secreted in the serum (P < 0.001) and ascites (P < 0.01). These results suggested that the targeted delivery of IL15 gene might be associated with its in vivo antitumor effects, which include inducing tumor cell apoptosis, inhibiting tumor proliferation and promoting the activation of immune cells such as T cells and natural killer cells. Furthermore, hematoxylin and eosin staining of vital organs following F-PLP/pIL15 treatment showed no detectable toxicity, thus indicating that intraperitoneal administration may be a viable route of delivery. Overall, these results suggest that F-PLP/pIL15 may serve as a potential targeting preparation for colon cancer therapy.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.10537